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MBE Advance Access published online on July 12, 2006

Molecular Biology and Evolution, doi:10.1093/molbev/msl060
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© 2006 The Authors This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Accepted July 4, 2006

Research Article

Feed Forward Loop Circuits as a Side Effect of Genome Evolution

Otto X. Cordero 1 * and Paulien Hogeweg 1

1 Theoretical Biology and Bioinformatics, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands

* To whom correspondence should be addressed.
Otto X. Cordero, E-mail: o.x.corderosanchez{at}bio.uu.nl


   Abstract

In this article we establish a connection between the mechanics of genome evolution and the topology of gene regulation networks, focusing in particular on the evolution of the Feed Forward Loop (FFL) circuits. For this we design a model of stochastic duplications, deletions and mutations of binding sites and genes and compare our results with yeast network data. We show that the mechanics of genome evolution may provide a mechanism of FFL circuit generation. Our simulations result in over-representation of FFL circuits as well as in their clustering around few regulator pairs, in concordance with data from transcription networks. The mechanism here proposed and the analysis of the yeast data show that regulator duplication could have played an important role in FFL evolution.

Keywords: Genome Evolution; Regulatory Networks; Mutational Dynamics; Network Motifs; Feed Forward Loop; Yeast.
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O. X. Cordero, B. Snel, and P. Hogeweg
Coevolution of gene families in prokaryotes
Genome Res., March 1, 2008; 18(3): 462 - 468.
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